Circulating kisspeptin and anti-müllerian hormone levels, and insulin resistance in women with polycystic ovary syndrome: A systematic review, meta-analysis, and meta-regression

Abstract

Objective: This systematic review and meta-analysis aimed to summarize the available evidence regarding circulating kisspeptin and anti-müllerian hormone (AMH) and the homeostasis model assessment of insulin resistance (HOMA-IR) index in adolescents and women with and without polycystic ovary syndrome (PCOS).

Method: We performed a comprehensive literature search in Medline, Embase, Cochrane, Scopus, and Web of Science for studies evaluating circulating kisspeptin levels in women with and without PCOS published until September 24th, 2020. Co-primary outcomes were the HOMA-IR index and AMH. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effects models were used to estimate outcomes, and effects reported as mean difference (MD) or standardized MD (SMD) and their 95 % confidence interval (CI). The systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42020205030.

Results: We evaluated 18 studies including, 1282 PCOS cases and 977 controls. Participants with PCOS were younger (MD = -2.38 years, 95 %CI -4.32 to -0.44), with higher BMI (MD = 1.16, 95 % CI 0.54-1.78), waist-to-hip ratio (MD = 0.04, 95 %CI 0.02 to 0.05), circulating kisspeptin (SMD = 1.15, 95 %CI 0.68-1.62), luteinizing hormone (SMD = 1.29, 95 %CI 0.76-1.83), AMH (SMD = 0.97, 95 %CI 0.60-1,34), total testosterone (SMD = 2.48, 95 %CI 1.73-3.23), free testosterone (SMD = 1.37, 95 %CI 0.56-2.17), and dehydroepiandrosterone sulphate (SMD = 0.72, 95 %CI 0.32-1.13) levels, and Ferriman-Gallwey score (SMD = 5.08, 95 %CI 2.76-7.39), and lower sex hormone-binding globulin level (SMD = -1.34, 95 %CI -2.15 to -0.52). Besides, participants with PCOS had higher HOMA-IR index (SMD = 0.76, 95 %CI 0.35-1.17), and circulating insulin (SMD = 0.75, 95 %CI 0.30-1.19), leptin (SMD = 2.82, 95 %CI 1.35-4.29), and triglycerides (SMD = 2.15, 95 %CI 1.08-3.23) levels than participants without the syndrome. The meta-regression did not identify significant factors influencing circulating kisspeptin.

Conclusion: Patients with PCOS showed higher kisspeptin, LH, insulin, AMH, and androgen levels and HOMA-IR index, and lower sex hormone-binding globulin levels than those without the syndrome.

Keywords: Anti-müllerian hormone; HOMA-IR; Insulin; Kisspeptin; Metastin; Polycystic ovary syndrome.